The Allostatic Model proposes that Alcohol Use Disorder (AUD) is associated with a transition in the motivational structure of alcohol drinking: from positive reinforcement in early-stage drinking to negative reinforcement in late-stage dependence. However, direct empirical support for this preclinical model from human experiments is limited. This study tests predictions derived from the Allostatic Model in humans. Specifically, this study tested whether alcohol use severity (1) independently predicts subjective responses to alcohol (SR; comprised of stimulation/hedonia, negative affect, sedation and craving domains), and alcohol self-administration and 2) moderates associations between domains of SR and alcohol self-administration. Heavy drinking participants ranging in severity of alcohol use and problems (N = 67) completed an intravenous alcohol administration paradigm combining an alcohol challenge (target BrAC = 60 mg%), with progressive ratio self-administration. Alcohol use severity was associated with greater baseline negative affect, sedation, and craving but did not predict changes in any SR domain during the alcohol challenge. Alcohol use severity also predicted greater self-administration. Craving during the alcohol challenge strongly predicted self-administration and sedation predicted lower self-administration. Neither stimulation, nor negative affect predicted self-administration. This study represents a novel approach to translating preclinical neuroscientific theories to the human laboratory. As expected, craving predicted self-administration and sedation was protective. Contrary to the predictions of the Allostatic Model, however, these results were inconsistent with a transition from positively to negatively reinforced alcohol consumption in severe AUD. Future studies that assess negative reinforcement in the context of an acute stressor are warranted.

中文翻译：

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酒精使用严重性方面，酒精的主观和动机特性上的差异：新型翻译型人类实验室范式的应用。

拟静力学模型提出，酒精使用障碍（AUD）与饮酒动机结构的转变有关：从早期饮酒的正强化到后期依赖的负强化。但是，来自人类实验的对该临床前模型的直接经验支持有限。这项研究测试了从人体中的同种异体模型得出的预测。具体而言，这项研究测试了酒精使用的严重性（1）是否独立预测对酒精的主观反应（SR；包括刺激/享乐症，负面影响，镇静和渴望域），以及酒精的自我给药；以及2）缓和SR域之间的关联和酒精自我管理。大量饮酒者因酒精使用的严重性和问题（N = 67）而完成了静脉酒精管理范例，该范例结合了酒精挑战（目标BrAC = 60 mg％）和逐步进行自我管理。酒精使用的严重程度与基线负面影响，镇静和渴望更大有关，但不能预测酒精攻击期间任何SR域的变化。饮酒的严重程度也预示着自我管理的增加。酒精挑战期间的渴望强烈预示了自我管理，而镇静则预示了较低的自我管理。刺激和消极因素均不会影响预期的自我管理。这项研究代表了一种将临床前神经科学理论转化为人体实验室的新颖方法。不出所料 渴望预测的自我管理和镇静具有保护作用。然而，与同构模型的预测相反，这些结果与重度AUD患者从正向增加酒精消费到负向增加酒精消费的转变不一致。将来有必要评估急性应激源下负强化的研究。